The purpose of this proposal is to advance use of the zebrafish as an applied tool for helping to diagnose and develop treatments for human disease. This proposal aims to develop and test a new method for using the zebrafish to measure the relative activity and potential pathogenicity of allelic forms of human genes. Methods will be developed that allow the removal of specific zebrafish genes on demand and the expression of human genes in the zebrafish. As a test case, this proposal uses the new methods to determine if the zebrafish can be used to distinguish between normal and disease-causing forms of the KCNH2 gene, a gene that when defective leads to Long QT Syndrome.